Folding domain B of protein A on a dynamically partitioned free energy landscape

The B domain of staphylococcal protein A (BdpA) is a small helical protein that has been studied intensively in kinetics experiments and detailed computer simulations that include explicit water. The simulations indicate that BdpA needs to reorganize in crossing the transition barrier to facilitate folding its C-terminal helix (H3) onto the nucleus formed from helices H1 and H2. This process suggests frustration between two partially ordered forms of the protein, but recent φ value measurements indicate that the transition structure is relatively constant over a broad range of temperatures. Here we develop a simplistic model to investigate the folding transition in which properties of the free energy landscape can be quantitatively compared with experimental data. The model is a continuation of the Muñoz-Eaton model to include the intermittency of contacts between structured parts of the protein, and the results compare variations in the landscape with denaturant and temperature to φ value measurements and chevron plots of the kinetic rates. The topography of the model landscape (in particular, the feature of frustration) is consistent with detailed simulations even though variations in the φ values are close to measured values. The transition barrier is smaller than indicated by the chevron data, but it agrees in order of magnitude with a similar α-carbon type of model. Discrepancies with the chevron plots are investigated from the point of view of solvent effects, and an approach is suggested to account for solvent participation in the model.